Core B will have three primary roles in the Program Project. First, Core B will be responsible for maintaining and supplying shared cell lines/cDNA constructs and antibodies for all investigators involved in the Program Project. Second, the Core will perform the Abeta ELISA for quantitating total Abeta, Abeta1-40, Abeta1-42, Abetax-40, and Abetax-42, in a timely and convenient manner for all investigators involved in the Program Project. Third, Core B will perform in vitro gamma-secretase activity assay on samples provided by all investigators involved in the Program Project. Specifically, Core B is intended to serve as a central repository for maintaining and supplying a large number of highly useful reagents that have been generated over the last decade by the Investigators involved in the Program Project. These reagents include a large variety of stably-transfected mammalian cell lines and corresponding transgene cDNA constructs, and an extensive collection of specific polyclonal and monoclonal antibodies. This should greatly facilitate ongoing collaborations and overall experimental efficiency within the Program Project. Extensive use of Core B Abeta ELISA by all Investigators in the past several years has generated multiple publications, and the quantitative measurement of Abeta will continue to be an indispensable part for almost all of the projects. Core B will be available to carry out the Abeta ELISA whenever desired by an Investigator. In addition, Core B will prepare a large quantity of purified gamma-secretase substrates C100Flag and N100Flag, which will be added to the testing samples provided by the Investigators. Core B will prepare HeLa cell lysates and include it in all gamma-secretase activity assays as positive control. Day-to-day operations of the Core B will be supervised by Dr. Weiming Xia and assisted by Dr. Dennis J. Selkoe and Dr. Rudolph E. Tanzi.